Synthesis and characterization of sugar containing hydrophilic and hydrophobic polymers with potential application in medicine

Dissertation toobtaina Master of Science degree in Bioorganics

Efeitos da laqueação proximal dos vasos curtos e da fundoplicatura total sobre a microcirculação do fundo gástrico : estudo microvascular em cobaias

RESUMO: A operação de Nissen, por laparoscopia, é considerada a cirurgia antirefluxo mais adequada por ser a que melhor replica a fisiologia normal da válvula gastresofágica na maioria dos doentes com sintomas típicos de doença do refluxo gastresofágico (DRGE). São critérios técnicos o encerramento seguro dos pilares do diafragma e a criação de fundoplicatura completa (360 graus), curta (inferior a dois centímetros), lassa e sem tensão – desiderando para o qual a laqueação proximal dos vasos curtos gástricos é crucial. Realizei a operação de Nissen, por laparoscopia, em sessenta mulheres e quarenta homens com DRGE, sem mortalidade operatória, no Serviço de Cirurgia 6 do Hospital dos Capuchos, CHLC, EPE. Os cem doentes apresentavam média etária de 46 anos e queixas, com tempo de evolução entre 1 e 43 anos, de pirose (90%), regurgitação (80%), azia (73%), epigastralgias (54%). A endoscopia alta revelou esofagite de grau Savary-Miller 0-I (62%), II (23%), III (8%), IV (7%); hérnia de deslizamento (71%), hérnia paraesofágica (8%), sem hérnia (21%); a pHmetria de 24h diagnosticou padrão misto (38%), levantado (20%), deitado (20%), inconclusiva (22%) e a manometria diagnosticou EEI hipotónico (35%), peristálise esofágica normal (88%), hipomotilidade ligeira (5%) e foi omissa (7%). Hérnia hiatal, esofagite grave, ineficácia do controlo sintomático com inibidor da bomba de protões e desejo de descontinuidade terapêutica constituíram as indicações para tratamento cirúrgico. Por celioscopia, efetuei laqueação dos vasos curtos gástricos (70%), cruroplastia e fundoplicatura total (seda 2/0), curta (dimensão média 1,5-2 cm), lassa, sem tensão e sem calibração intraoperatória do esófago. A fundoplicatura de Nissen laparoscópica mostrou-se segura e eficaz no tratamento da DRGE. A sua idoneidade foi ainda comprovada pela normalização da pHmetria de 24 horas e da manometria pós-operatórias, com significado estatístico, num grupo de catorze voluntários assintomáticos. Em catamnese com recuo médio 30,7 meses 94% dos indivíduos persistem assintomáticos. Interrogando-me acerca das repercussões desta operação sobre a microcirculação do fundo gástrico coloquei, como premissa, a possibilidade de na operação de Nissen a laqueação dos vasos curtos poder induzir modificação no diâmetro arteriolar da parede do fundo gástrico. Para pesquisar a influência da laqueação dos vasos curtos gástricos e da fundoplicatura total sobre o calibre arteriolar da parede do estômago no cárdia, no fundo e na região dos vasos curtos gástricos, idealizei um Projeto de investigação experimental em cobaias. O Projeto foi desenvolvido no Centro de Investigação do Departamento de Anatomia da FCM-UNL. Para a sua realização obtive autorização da Comissão Científica e Pedagógica da FCM-UNL, requeri a acreditação como investigador à Direção Geral de Veterinária e, por recorrer à utilização de animais, submeti-o à Comissão de Ética da FCM-UNL, que o aprovou por unanimidade. Para limitar o número de animais utilizados ao mínimo necessário, calculei, por método estatístico, a quantidade de cobaias necessárias. Subdividindo-as num grupo de ensaio (GE), onde realizei a operação de Nissen, e num grupo de controlo (GC), onde apenas procedi a tração gástrica, defini e apliquei protocolos de anestesia, de cirurgia e de eutanásia, segundo os princípios dos 3R – Replacement, Reduction, Refinement da técnica de experimentação humana de Russell e Burch (1959) – uma estrutura ética amplamente aceite para a realização de experimentação científica humanizada com animais. A utilização das técnicas de estudo angiomorfológico permitiu-me analisar e descrever a anatomia normal, a vascularização arterial macroscópica, a microangioarquitetura, por microscopia eletrónica de varrimento de moldes de corrosão vascular, e a histologia da parede do estômago da cobaia. Procedi, também, à definição dos critérios morfológicos que considerei suscetíveis de validação deste modelo animal para o estudo proposto. Por razões académicas, foi necessário abreviar o Projeto encurtando, em cerca de dois anos, o prazo disponível para conclusão do estudo. Apreciando-o com o Gabinete de Análise Epidemiológica e Estatística do Centro de Investigação do CHLC, EPE, optou-se, perante a escassez de elementos após já terem sido recrutados 46 animais, por uma amostra, suplementar, de dimensão de conveniência de oito cobaias (quatro em cada grupo), condicionada pelo limite temporal universitário e pelo respeito pela dignidade dos animais. Neste subgrupo procedi, por microscopia eletrónica de varrimento, à medição dos calibres arteriolares nos moldes vasculares do cárdia, do fundo e da zona dos vasos curtos gástricos tanto no GC como no GE efetuando 469 medições no primeiro e 461 no último. Os dados foram enviados ao Centro de Investigação do CHLC, EPE que procedeu à sua análise estatística (ANOVA). A referida análise revelou que as arteríolas do plexo mucoso e as do plexo submucoso do cárdia, do fundo e da região dos vasos curtos gástricos, mostraram aumento de calibre no GE. O aumento foi, estatisticamente, significativo por ser superior a 50% do calibre do GC. Nos vasos curtos, a diferença foi mais pequena, mas persistiu sendo, estatisticamente, significativa. Os vasos retos dilataram na base, na sua emergência do plexo seroso, apenas no fundo gástrico. Na cobaia a operação de Nissen – fundoplicatura total com laqueação dos vasos curtos gástricos –, provocou vasodilatação arteriolar do fundo gástrico. Considero que essa vasodilatação constituiu acomodação à modificação introduzida e infiro que o mesmo possa acontecer no ser humano. Admito, assim, que também ocorra vasodilatação no ser humano, na sequência da laqueação dos vasos curtos gástricos, pela analogia microvascular entre as duas espécies e que essa vasodilatação corresponda, igualmente, a um mecanismo de adaptação arteriolar visando, por exemplo, suprir a perda incorrida pela laqueação. A associação experimental entre laqueação dos vasos curtos gástricos e realização de fundoplicatura total, que exerce aumento inerente de pressão sobre a JEG, não só não provocou défice da microcirculação do esófago distal ou do estômago proximal como desencadeou um mecanismo de vasodilatação fúndica que reforça o conceito de segurança da operação de Nissen para tratamento da DRGE. -------------- ABSTRACT: The laparoscopic Nissen operation is considered to be the most appropriate antirefluxsurgery because it suitably replicates the standard physiology of the gastroesophageal valve in most patients with typical symptoms of gastroesophageal reflux disease (GERD). The technical criteria includes the safe shutdown of the diafragmatic crura(cruroplasty) and the creation of a complete fundoplication (360 degrees), short (lesser than two inches), floppy and without tension – a goal for which the proximal ligation of the gastric short vessels is crucial. The laparoscopic Nissen operation was performed in sixty women and forty men with GERD, without any operative mortality, at the Surgical Department of the Hospital dos Capuchos, CHLC, EPE. The one hundred patients, averaged 46 years old, complained of heartburn (90%), regurgitation (80%) and upper abdominal pain (54 %). The endoscopy process revealed Savary-Miller esophagitis of grade 0-I (62%), II (23%), III (8%), IV (7%), sliding hernia (71%), paraesophageal hernia (8%) or no herniation (21%). The pHmetry/24h diagnosed mixed pattern (38%), raised (20%), lying (20%) or inconclusive (22%). The manometry diagnosed hypotensive LES (35%), normal esophageal peristalsis (88%), mild hypomotility (5%) and was absent (7%). Hiatal hernia, severe esophagitis, ineffective symptomatic control with proton pump inhibitor and request for treatment discontinuation were the signs for surgical action. A laparoscopic ligation of short gastric vessels (70%), cruroplasty and fundoplication (silk 2/0), short (average size 1.5–2 cm) and floppy, without tension and without intraoperative calibration of the esophagus were thus performed. The laparoscopic Nissen fundoplication behaved safe and effective in treating GERD. In a group of 14 asymptomatic volunteers its reputation was confirmed with statistical significance by normalization of postoperative pHmetry/24h and manometry. 94% of the individuals remained asymptomatic up to 30.7 months (average) in the follow-up. Interrogating myself about the impact of this operation on the microcirculation of the gastric fundus I put premised on the possibility of the ligation of the short gastric vessels in the Nissen procedure can induce changes in the arteriolar diameter in the Wall of the gastric fundus. To explore the influence of ligation of the short gastric vessels and the fundoplication at the arteriolar caliber of the cardia, the fundus and the region of the short vessels of the gastric wall, I designed a project of experimental research in guinea pigs with two interdependent components: one veterinary and another technical where I applied angiomorphological studies. The project was developed at the Research Centre of the Department of Anatomy FCMUNL. For its accomplishment I got permission from the Scientific and Pedagogical Committee of the FCM-UNL, I requested for accreditation as a researcher at the General Directorate of Veterinary and, by resorting to the use of animals I submitted it to the Ethics Committee of the FCM-UNL, which approved it unanimously. The guinea pigs were divided into two experimental groups: an experimental group (EG), in which the Nissen procedure was performed and a control group (CG) in which only a gastric traction was done. Protocols of anesthesia, surgery and euthanasia were applied according to the 3Rs – Replacement, Reduction, Refinement of the technique of human experimentation of Burch and Russell (1959) – a widely accepted ethical framework for conducting scientific experiments using animals humanely. Using histological and angiomorphological techniques, I performed the analysis and the description of the normal, macro and microvascular, anatomy of the guinea pig stomach and I defined the morphological criteria that I considered susceptible for validation of this animal model for the proposed study. By means of scanning electron microscopy I measured the arteriolar calibers of the vascular casts of the cardia, of the fundus and of the short gastric vessels in both CG and EG, making 469 measurements in the former and 461 in the latter. The data were sent to the Research Center of the CHLC which conducted the statistical analysis (ANOVA). The data were sent to the Centre for Research of the CHLC, EPE which proceeded to statistical analysis (ANOVA). This analysis revealed that the arterioles plexus of the mucosal and submucosal plexus of the cardia, fundus and region of the short gastric vessels, showed increased caliber in EG. The increase was statistically significant for being greater than 50% CG gauge. In the short gastric vessels, the difference was smaller, but persisted and statistically significant. Straight vessels were dilated at the base, on its emergence of the plexus serous only in the fundus. In the guinea pig, the Nissen procedure - complete fundoplication with ligation of the short gastric vessels - caused arteriolar vasodilation on the gastric fundus. I believe that this vasodilation constituted some accommodation to the modification introduced and infer that the same might happen in humans. I admit therefore that vasodilation also occurs in humans following the ligation of the short gastric vessels by microvascular analogy between the two species and that this vasodilation corresponds also to na adaptation mechanism arteriolar, for example, to compensate the loss incurred by ligation. The association of experimental ligation of the short gastric vessels with conducting complete fundoplication, which exerts increased pressure on the EGJ, not only did not cause a microcirculation deficit of the distal esophagus or proximal stomach as triggered a mechanism of fundic vasodilation which reinforces the security concept of the Nissen procedure for treatment of GERD.

Supercomplexes of Prokaryotic Aerobic Respiratory Chains-Escherichia coli and Bacillus subtilis supramolecular assemblies

Dissertation presented to obtain the Ph.D degree in Biochemistry.

The effect of social and environmental sustainability on firm resilience

Double degree

Development and modulation of magnetic responsive supported ionic liquid membranes

The work presented in this thesis aims at developing a new separation process based on the application of supported magnetic ionic liquid membranes, SMILMs, using magnetic ionic liquids, MILs. MILs have attracted growing interest due to their ability to change their physicochemical characteristics when exposed to variable magnetic field conditions. The magnetic responsive behavior of MILs is thus expected to contribute for the development of more efficient separation processes, such as supported liquid membranes, where MILs may be used as a selective carrier. Driven by the MILs behavior, these membranes are expected to switch reversibly their permeability and selectivity by in situ and non-invasive adjustment of the conditions (e.g. intensity, direction vector and uniformity) of an external applied magnetic field. The development of these magnetic responsive membrane processes were anticipated by studies, performed along the first stage of this PhD work, aiming at getting a deep knowledge on the influence of magnetic field on MILs properties. The influence of the magnetic field on the molecular dynamics and structural rearrangement of MILs ionic network was assessed through a 1H-NMR technique. Through the 1H-NMR relaxometry analysis it was possible to estimate the self-diffusion profiles of two different model MILs, [Aliquat][FeCl4] and [P66614][FeCl4]. A comparative analysis was established between the behavior of magnetic and non-magnetic ionic liquids, MILs and ILs, to facilitate the perception of the magnetic field impact on MILs properties. In contrast to ILs, MILs show a specific relaxation mechanism, characterized by the magnetic dependence of their self-diffusion coefficients. MILs self-diffusion coefficients increased in the presence of magnetic field whereas ILs self-diffusion was not affected. In order to understand the reasons underlying the magnetic dependence of MILs self-diffusion, studies were performed to investigate the influence of the magnetic field on MILs’ viscosity. It was observed that the MIL´s viscosity decreases with the increase of the magnetic field, explaining the increase of MILs self-diffusion according to the modified Stokes- Einstein equation. Different gas and liquid transport studies were therefore performed aiming to determine the influence of the magnetic behavior of MILs on solute transport through SMILMs. Gas permeation studies were performed using pure CO2 andN2 gas streams and air, using a series of phosphonium cation based MILs, containing different paramagnetic anions. Transport studies were conducted in the presence and absence of magnetic field at a maximum intensity of 1.5T. The results revealed that gas permeability increased in the presence of the magnetic field, however, without affecting the membrane selectivity. The increase of gas permeability through SMILMs was related to the decrease of the MILs viscosity under magnetic field conditions.(...)

Differential top-antitop cross-section measurements as a function of observables constructed from final-state particles using pp collisions at s√=7 TeV in the ATLAS detector

Various differential cross-sections are measured in top-quark pair (tt¯) events produced in proton--proton collisions at a centre-of-mass energy of s√=7 TeV at the LHC with the ATLAS detector. These differential cross-sections are presented in a data set corresponding to an integrated luminosity of 4.6 fb−1. The differential cross-sections are presented in terms of kinematic variables of a top-quark proxy referred to as the pseudo-top-quark whose dependence on theoretical models is minimal. The pseudo-top-quark can be defined in terms of either reconstructed detector objects or stable particles in an analogous way. The measurements are performed on tt¯ events in the lepton+jets channel, requiring exactly one charged lepton and at least four jets with at least two of them tagged as originating from a b-quark. The hadronic and leptonic pseudo-top-quarks are defined via the leptonic or hadronic decay mode of the W boson produced by the top-quark decay in events with a single charged lepton.The cross-section is measured as a function of the transverse momentum and rapidity of both the hadronic and leptonic pseudo-top-quark as well as the transverse momentum, rapidity and invariant mass of the pseudo-top-quark pair system. The measurements are corrected for detector effects and are presented within a kinematic range that closely matches the detector acceptance. Differential cross-section measurements of the pseudo-top-quark variables are compared with several Monte Carlo models that implement next-to-leading order or leading-order multi-leg matrix-element calculations.

Measurement of Spin Correlation in Top-Antitop Quark Events and Search for Top Squark Pair Production in pp Collisions at s√=8 TeV Using the ATLAS Detector

A measurement of spin correlation in tt¯ production is presented using data collected with the ATLAS detector at the Large Hadron Collider in proton-proton collisions at a center-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 20.3 fb−1. The correlation between the top and antitop quark spins is extracted from dilepton tt¯ events by using the difference in azimuthal angle between the two charged leptons in the laboratory frame. In the helicity basis the measured degree of correlation corresponds to Ahelicity=0.38±0.04, in agreement with the Standard Model prediction. A search is performed for pair production of top squarks with masses close to the top quark mass decaying to predominantly right-handed top quarks and a light neutralino, the lightest supersymmetric particle. Top squarks with masses between the top quark mass and 191 GeV are excluded at the 95% confidence level.

Observation of top-quark pair production in association with a photon and measurement of the t t ¯ γ production cross section in pp collisions at s =7 TeV using the ATLAS detector

A search is performed for top-quark pairs (tt¯) produced together with a photon (γ) with transverse momentum >20 GeV using a sample of tt¯ candidate events in final states with jets, missing transverse momentum, and one isolated electron or muon. The dataset used corresponds to an integrated luminosity of 4.59 fb−1 of proton--proton collisions at a center-of-mass energy of 7 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. In total 140 and 222 tt¯γ candidate events are observed in the electron and muon channels, to be compared to the expectation of 79±26 and 120±39 non-tt¯γ background events respectively. The production of tt¯γ events is observed with a significance of 5.3 standard deviations away from the null hypothesis. The tt¯γ production cross section times the branching ratio (BR) of the single-lepton decay channel is measured in a fiducial kinematic region within the ATLAS acceptance. The measured value is σfidtt¯γ=63±8(stat.)+17−13(syst.)±1(lumi.) fb per lepton flavor, in good agreement with the leading-order theoretical calculation normalized to the next-to-leading-order theoretical prediction of 48±10 fb.

Search for direct pair production of a chargino and a neutralino decaying to the 125 GeV Higgs boson in root s=8 TeV pp collisions with the ATLAS detector

A search is presented for the direct pair production of a chargino and a neutralino pp→χ~±1χ~02, where the chargino decays to the lightest neutralino and the W boson, χ~±1→χ~01(W±→ℓ±ν), while the neutralino decays to the lightest neutralino and the 125 GeV Higgs boson, χ~02→χ~01(h→bb/γγ/ℓ±νqq). The final states considered for the search have large missing transverse momentum, an isolated electron or muon, and one of the following: either two jets identified as originating from bottom quarks, or two photons, or a second electron or muon with the same electric charge. The analysis is based on 20.3 fb−1 of s√=8 TeV proton-proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with the Standard Model expectations, and limits are set in the context of a simplified supersymmetric model.

Search for H→γγ produced in association with top quarks and constraints on the Yukawa coupling between the top quark and the Higgs boson using data taken at 7 TeV and 8 TeV with the ATLAS detector

A search is performed for Higgs bosons produced in association with top quarks using the diphoton decay mode of the Higgs boson. Selection requirements are optimized separately for leptonic and fully hadronic final states from the top quark decays. The dataset used corresponds to an integrated luminosity of 4.5 fb−1 of proton--proton collisions at a center-of-mass energy of 7 TeV and 20.3 fb−1 at 8 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. No significant excess over the background prediction is observed and upper limits are set on the tt¯H production cross section. The observed exclusion upper limit at 95% confidence level is 6.7 times the predicted Standard Model cross section value. In addition, limits are set on the strength of the Yukawa coupling between the top quark and the Higgs boson, taking into account the dependence of the tt¯H and tH cross sections as well as the H→γγ branching fraction on the Yukawa coupling. Lower and upper limits at 95% confidence level are set at −1.3 and +8.0 times the Yukawa coupling strength in the Standard Model.

Search for Higgs Boson Pair Production in the γγbb¯ Final State using pp Collision Data at s√=8TeV from the ATLAS Detector

Searches are performed for resonant and non-resonant Higgs boson pair production in the hh→γγbb¯ final state using 20 fb−1 of proton--proton collisions at a center-of-mass energy of 8TeV recorded with the ATLAS detector at the CERN Large Hadron Collider. A 95% confidence level upper limit on the cross section times branching ratio of non--resonant production is set at 2.2 pb, while the expected limit is 1.0 pb. The corresponding limit observed for a narrow resonance ranges between 0.8 and 3.5 pb as a function of its mass.

Search for massive supersymmetric particles decaying to many jets using the ATLAS detector in pp collisions at s√=8TeV

Results of a search for decays of massive particles to fully hadronic final states are presented. This search uses 20.3 fb−1 of data collected by the ATLAS detector in s√=8TeV proton--proton collisions at the LHC. Signatures based on high jet multiplicities without requirements on the missing transverse momentum are used to search for R-parity-violating supersymmetric gluino pair production with subsequent decays to quarks. The analysis is performed using a requirement on the number of jets, in combination with separate requirements on the number of b-tagged jets, as well as a topological observable formed from the scalar sum of the mass values of large-radius jets in the event. Results are interpreted in the context of all possible branching ratios of direct gluino decays to various quark flavors. No significant deviation is observed from the expected Standard Model backgrounds estimated using jet-counting as well as data-driven templates of the total-jet-mass spectra. Gluino pair decays to ten or more quarks via intermediate neutralinos are excluded for a gluino with mass mg~<1TeV for a neutralino mass mχ~01=500GeV. Direct gluino decays to six quarks are excluded for mg~<917GeV for light-flavor final states, and results for various flavor hypotheses are presented.

Search for new phenomena in events with a photon and missing transverse momentum in pp collisions at s√=8 TeV with the ATLAS detector

Results of a search for new phenomena in events with an energetic photon and large missing transverse momentum with the ATLAS experiment at the LHC are reported. Data were collected in proton--proton collisions at a center-of-mass energy of 8 TeV and correspond to an integrated luminosity of 20.3 fb−1. The observed data are well described by the expected Standard Model backgrounds. The expected (observed) upper limit on the fiducial cross section for the production of such events is 6.1 (5.3) fb at 95% confidence level. Exclusion limits are presented on models of new phenomena with large extra spatial dimensions, supersymmetric quarks, and direct pair production of dark-matter candidates.

Variáveis geomorfométricas locais e sua relação com a vegetação da região do interflúvio Madeira-Purus (AM-RO)

O presente trabalho teve como objetivo avaliar o potencial das variáveis geomorfométricas extraídas de dados SRTM (Shuttle Radar Topographic Mission) para identificação de tipos vegetacionais da região do interflúvio Madeira-Purus. As variáveis geomorfométricas (elevação, declividade, orientação de vertente, curvatura vertical e curvatura horizontal) foram confrontadas com o mapa de vegetação do projeto RADAMBRASIL através de análises de histogramas e análises discriminantes. Tais análises indicaram os grupos de classes vegetacionais que podem ser separados mais facilmente em contraste com outros grupos que ocorrem sob as mesmas condições topográficas. As variáveis de relevo mais importantes na distinção entre os tipos vegetacionais foram: a elevação, a declividade e a orientação de vertentes. Apesar dos dados geomorfométricos mostrarem potencial indicativo das classes de vegetação, as análises resultaram em discriminação em um nível aquém do detalhamento temático máximo apresentado pelos dados RADAM. Tal desempenho pode ser explicado pela incompatibilidade das escalas de variação exibidas entre os dados geomorfométricos em relação ao tamanho das unidades de mapeamento da vegetação, além da co-ocorrência de classes de respostas distintas ao relevo sob uma mesma associação de classes sob as mesmas classes na legenda. Com base nas análises discriminantes das variáveis geomorfométricas, foi possível o mapeamento da vegetação experimentalmente até o nível de subfisionomias.

Search for new phenomena in the dijet mass distribution using pp collision data at s√=8 TeV with the ATLAS detector

Dijet events produced in LHC proton--proton collisions at a center-of-mass energy s√=8 TeV are studied with the ATLAS detector using the full 2012 data set, with an integrated luminosity of 20.3 fb−1. Dijet masses up to about 4.5 TeV are probed. No resonance-like features are observed in the dijet mass spectrum. Limits on the cross section times acceptance are set at the 95% credibility level for various hypotheses of new phenomena in terms of mass or energy scale, as appropriate. This analysis excludes excited quarks with a mass below 4.09 TeV, color-octet scalars with a mass below 2.72 TeV, heavy W′ bosons with a mass below 2.45 TeV, chiral W∗ bosons with a mass below 1.75 TeV, and quantum black holes with six extra space-time dimensions with threshold mass below 5.82 TeV.